Bioactive carrier

Abstract

Bioactive carrier for the settlement of living cells, comprising a porous three-dimensional web framework (2) made of glass, characterized by a porous reinforcement structure (3) made of a synthetic polymer that is soluble in the human or animal body, wherein the reinforcement structure (3) is a fiber structure (4) surrounding the web framework (2) on the outside.

Description

[0001] The invention relates to a bioactive carrier for the settlement of living cells, comprising a porous three-dimensional framework made of glass.

[0002] Osteoarthritis is a common joint disease of significant economic importance due to the resulting treatment costs and work disability. Its significance is increasing in light of current demographic changes. It is currently incurable and characterized by a progressive course, during which the cartilage in the joints is attacked, loses its strength, and is partially destroyed. Osteoarthritis often develops as a consequence of injuries to the articular cartilage, as articular cartilage and cartilage tissue in general have very limited self-healing capacity. The only treatment option for reconstructing the joint surfaces after cartilage damage and in advanced osteoarthritis is often surgical intervention, which frequently involves partial or total joint replacement with an implant.Alternatively, the possibility of cultivating suitable autologous cartilage tissue in vitro as a biological replacement is being pursued. Once cultivated, this replacement tissue is transplanted into the patient's cartilage defect to replace the damaged articular cartilage.

[0003] To ensure a three-dimensional arrangement of the cartilage cells, natural and synthetic biomaterials are used, which are designed to dissolve once tissue regeneration has progressed in the defect.

[0004] This method of tissue generation through the cultivation of cultured cells in a suitable biomaterial is called "tissue engineering." Here, cell proliferation of adherent cells is first achieved in vitro, i.e., in a cell culture, followed by tissue formation on a three-dimensional bioactive substrate. To achieve this in vitro growth of cartilage cells, so-called chondrocytes, cells taken from the body must be stimulated in a suitable environment. An appropriate geometric arrangement of the cells can support the formation of the new tissue. Several fundamental factors are of high importance for the in vitro growth of the cells and tissue formation: A suitable open-pored scaffold with a porosity of at least 60% is required for cell growth; that is, a bioactive support that not only meets the mechanical requirements placed on such a support in the future tissue, but is also sufficiently cyto- and biocompatible to ensure cell survival and not trigger inflammation.

[0005] Living and proliferating cells must be able to adhere to the bioactive support, the so-called scaffold. This means that sufficient cell adhesion to the scaffold must be possible. Therefore, the cell surface receptors must recognize structures in the scaffold as binding motifs, and the necessary cofactors (including ions) must be sufficiently available.

[0006] Furthermore, it must be possible to stimulate and control cell-type-specific signal transduction in living cells, which can be achieved, for example, through growth stimulators (such as growth factors, ions, but also a suitable scaffold topology).

[0007] Finally, for initial cell proliferation, i.e., cell multiplication and cell growth, as well as subsequent differentiation of the cells, a conducive extracellular environment must be present in the scaffold and around the cells.

[0008] Of particular interest is the synthesis of a new extracellular cartilage matrix by the cells within the scaffold, a process controlled by factors including the geometric scaffold structure (topology) and growth factors, since articular cartilage consists of over 90% extracellular matrix (ECM). The stimulating factors for cell growth and matrix synthesis can be broadly categorized as electrochemical / biochemical, structure-associated, and mechanical. For optimal cell proliferation, these factors must be selected to suit the specific cell type being cultivated.

[0009] Within the framework of tissue engineering, the bioactive scaffold is a central element, as it must be mechanically stable while simultaneously enabling cell adhesion, cell growth, and ECM synthesis. It must also be degradable, whereby the resulting concentration gradients of ions with corresponding chemical and electrochemical potentials, created by dissolving the bioactive scaffold, can support cell proliferation, cell differentiation, and ECM synthesis. Glass is considered an excellent material for the fabrication of such a bioactive scaffold in this context.

[0010] Such bioactive scaffolds, also called bioglasses, are known in various applications, for example from WO 2011 / 161422 A1, WO 2016 / 089731 A1, or WO 2014 / 168631 A1. These publications deal explicitly with the production of a scaffold. The bioactive scaffolds or bioglasses described therein are based on alkaline earth and phosphate-containing glass systems that form a hydroxyapatite layer on the glass surface in aqueous solutions. This hydroxyapatite layer forms an interface, a so-called boundary layer, to which the living cells to be multiplied must adhere and which is intended to promote growth. The best-known of these alkaline earth bioglasses is known as 45 S5.

[0011] German patent application DE 10 2018 114 946 B3 describes a bioactive glass support that exhibits excellent properties with regard to bioactivity and the geometry required for good cell growth. The bioactivity is achieved through leaching of the surface layer of the glass scaffold, resulting in gel formation on the surface. Due to the leaching process and the resulting reduction in the content of alkali metal oxides in the leached surface, as well as the incorporation of OH groups and water into the leached "open" network in the leached area, the corresponding structural units within the glass matrix are only weakly linked.

[0012] This leads to reduced chemical stability and promotes the dissolution of the support during in vivo use; that is, the glass support dissolves due to the hydrolytic acid-base attack of the surrounding medium during in vivo use. This solubility, or biodegradation, is a key property of any bioactive glass support when used in vivo.

[0013] The specific glass structures of such a bioactive carrier, as known, for example, from DE 10 2018 114 946 B3, are characterized by very thin struts within the porous, three-dimensional framework, which are essential for the framework's strength. For the formation of an open-pored, quasi-sponge-like structure, strut thicknesses of 10–400 µm are preferred, meaning that the framework is very finely structured. Therefore, the strength of such glass structures is limited, particularly during glass dissolution in in vivo applications, which, as described, is desirable. However, a certain degree of strength is required for implant use to prevent short-term shear and compressive loads from causing the structure to separate and thus destroy the implant.In in vivo use, the strength of the implant is not solely defined by the inorganic framework, but also by the ECM, which is intended to absorb some of the mechanical load; however, the mechanical strength of the support or framework also plays a role.

[0014] WO 2004 / 049904 A2 describes a bioactive carrier produced by weaving a glass thread or bundle of threads, whereby polymer threads or bundles of polymer threads can also be woven in alongside the glass thread. The three-dimensional carrier is produced either by layering and stitching several two-dimensional fabrics together. A porous structure can be created by needle punching. Alternatively, the three-dimensional carrier can also be produced by folding a two-dimensional fabric. This carrier does not have a porous, three-dimensional framework.

[0015] The publication by Rahaman, M. et al., “Review - bioactive glass implants for potential applications in structural bone repair”, Biomed. Glasses, 3, pp. 56-66, 2017, describes a bioactive scaffold that can consist of a three-dimensional porous framework. Reinforcement is achieved by coating the scaffold structure with a biodegradable polymer to increase stiffness; that is, the scaffold, or its glass webs, are coated externally and encased with the polymer. This polymer thus becomes part of the glass or web scaffold itself.

[0016] DE 10 2018 114 946 B3 discloses a bioactive carrier with a porous three-dimensional web framework made of glass, which has no reinforcing structure.

[0017] The publication by Mantsos, T. et al., “Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(D,L-lactide acid) coatings”, Biomed. Mater. 4, pp. 1-12, 2009, also reveals a porous glass web scaffold as the support base. Here, too, the glass web scaffold is coated with a biodegradable polymer, meaning that the polymer coating of the glass webs or the scaffold is not an independent reinforcing structure, but rather an integral part of the scaffold structure.

[0018] The invention is therefore based on the problem of specifying an improved bioactive carrier in comparison.

[0019] To solve this problem, a porous reinforcement structure made of a synthetic polymer that is soluble in the human or animal body is provided according to the invention for a bioactive carrier of the type mentioned above, according to claim 1 or claim 6.

[0020] The bioactive carrier according to the invention is characterized by an additional reinforcing structure that serves to strengthen or stiffen the carrier itself, thus giving it, as a whole, higher mechanical strength, so that it is able to withstand higher loads for short periods without the web framework separating or breaking. In addition to the glass web framework, which, with regard to in vivo use, can of course also be dissolved in the human or animal body over a corresponding period of time, a similarly porous reinforcing structure is provided on the web framework. This structure consists of a synthetic polymer that is also cell-compatible and therefore non-toxic, and thus dissolves in the human or animal body.Like the web framework, the reinforcement structure is also porous in order to maintain the property of the support as a quasi-sponge-like structure and to allow the settlement of cells within the entire volume of the three-dimensional support.

[0021] While a purely unreinforced scaffold collapses under compressive stress due to continuous breakage of the struts, it has been shown—as will be discussed further below—that applying such a polymer reinforcement structure significantly improves the strength and resistance of the bioactive support to such mechanical stress. This is because the support exhibits quasi-elastic properties, retaining its shape under load and resisting the stress. In other words, the glass scaffold remains essentially intact and does not break into its individual components, thus stabilizing the glass scaffold and achieving increased resistance to compressive stress and compression.

[0022] This polymer reinforcement therefore enables the realization of an implant that has improved resistance to external stresses and gives the bioactive carrier dimensional stability with elastic behavior, without impairing the advantageous properties of the bioglass.

[0023] As mentioned, any bioglass that is fundamentally soluble in the human or animal body and that allows the colonization of living cells can be used as the glass for forming the three-dimensional rib framework. In addition to glasses such as those already described in the introduction, the bioglass described in DE 10 2018 114 946 B3 is particularly suitable, as it can be provided with the polymer reinforcement structure according to the invention and exhibits excellent support properties due to the surface leaching of the rib framework, which can occur before or after application of the polymer reinforcement.

[0024] A key property of polymer reinforcement structures, besides providing the necessary strength and resistance to mechanical stress, is the polymer's solubility in the human or animal body, i.e., in vivo use. This means that the polymer must be biodegradable, and that no toxic substances that could impair cell growth or destroy existing cells should be emitted during this degradation process. One polymer that has proven particularly suitable for this purpose is a polymer from the polylactide group, specifically polylactic acid (PLA). These are synthetic polymers belonging to the polyester class and are composed of many chemically bonded lactic acid molecules. Their molecular structure makes them highly biodegradable, which is an important factor for in vivo applications.

[0025] Among the polylactides, poly(L-lactide), poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide), and poly(D,L-lactide-co-glycolide) are particularly suitable for producing the reinforcing structure. The table below shows the approximate degradation rates in the human body and the inherent viscosity, which is a measure of the material's elasticity, for the suitable biodegradable synthetic polymers. composition Degradation rate in the human body “Inherent viscosity” [dl / g] Poly(L-lactide) longer than 2 years 0,8-4,3 Poly(L-lactide-co-glycolide) 1-2 years 1,7-7,0 Poly(L-lactide-co-D,L-lactide) 2-3 years 2,0-6,5 Poly(D,L-lactide) 5 months - 2 years 0,16-1,7 Poly(D,L-lactide-co-glycolide) 5 - 9 months 0,14-1,7

[0026] According to a first alternative of the invention, the reinforcing structure is a fiber structure surrounding the web framework on the outside. Accordingly, the reinforcing structure is attached to the outside of the web framework, essentially enclosing or surrounding it. This outer reinforcing structure is elastic and offers corresponding resistance to external loads, thus protecting the inner web framework.

[0027] According to the invention, the reinforcing structure can be designed in the form of a wrapping around the web framework. This means that a thin polymer fiber is spun around the web framework, surrounding it like a very open-pored cocoon, with the fibers only making contact with the web framework at specific points. Preferably, the wrapping is applied in such a way that the web framework is completely enclosed.

[0028] The over-spinning, as described, is to be applied in such a way that the open-pore structure is maintained. Preferably, the over-spinning or fiber structure is applied such that the surface area it covers is a maximum of 10%. This means that 90% or more of the area enclosing the web framework is not over-spinned, so that over 90% of the surface of the outer surface defined by the web framework remains open, allowing for the introduction of the nutrient solution and cell growth inside without problems.

[0029] The fibers of the fiber structure itself preferably have a diameter of 2 - 100 µm, in particular of 5 - 75 µm and preferably of 10 - 50 µm, meaning that they are extremely fine fibers.

[0030] While, according to the first alternative of the invention, the reinforcing structure is applied to the outside of the web structure, according to a second alternative of the invention, a fiber structure formed inside the web framework is applied as the reinforcing structure. Here, the reinforcing structure is formed within the volume of the glass framework. The fibers forming the reinforcing structure extend between the webs, and may optionally extend over several webs. Preferably, the fiber structure forms a fiber framework structure that is at least partially continuous, meaning that not only do individual fibers extend between the webs, stiffening them, but a true polymer framework is formed within the glass framework as an additional stiffening structure.

[0031] Here too, the stiffening structure, for example the polymer framework, increases strength, so that in the event of a load the glass framework does not collapse in on itself, but rather, due to the elastic properties of the reinforcing structure, resistance is offered to the load, so that the support has a certain elasticity and is able to absorb any loads.

[0032] Even with this second inventive alternative, a high degree of porosity is maintained despite the integration of the reinforcement structure in order to enable cell growth within the carrier. The porosity of the carrier should be at least 80% despite the integrated reinforcement structure or polymer scaffold.

[0033] Although either the outer or the inner fiber structure can be applied as the reinforcement structure from the two alternatives described above, it is also conceivable according to the invention to provide both an outer and an inner fiber structure, thus combining both reinforcement techniques. For example, the inner fiber structure, i.e., the continuous polymer framework within the glass framework, is formed first, after which the outer reinforcement structure is applied by wrapping in a second step. The porosity remains sufficient to populate the substrate volume with cells, and the strength of the substrate is even greater in this case than when only one type of reinforcement structure is applied.

[0034] The web framework itself should have a porosity of at least 80%, preferably more, whereby, as explained, the overall porosity of the beam is only slightly reduced by the application of the appropriate stiffening structures.

[0035] The pore size of the web framework should be between 20 - 300 µm, in particular between 50 - 200 µm, while the webs of the web framework can have a thickness of 10 - 400 µm, in particular 20 - 200 µm and preferably between 50 - 150 µm.

[0036] The framework itself can be manufactured in various ways. One possibility is to produce the framework from glass fibers bonded together by sintering. Here, individual glass fibers, either individually or, for example, in the form of prefabricated glass fiber mats or rovings, are layered on top of each other and bonded together at the contact points by sintering, thus forming a corresponding glass framework. Using such glass fibers, it is possible to produce various support geometries, for example, in the form of plates, rectangular or square cubes, trapezoidal or spherical shapes, but also hollow bodies such as tubes or the like.This is because the glass fibers can be laid in different geometries and then sintered together, which makes it possible to design the basic shape of the bioactive carrier with regard to the desired geometry of the finished, seeded implant.

[0037] As an alternative to using glass fibers, which are naturally very thin depending on the desired web thickness, a second alternative for manufacturing the web framework involves producing it from sintered glass powder. In this alternative, for example, a polymer support structure is used, which is coated with a glass powder suspension. In a subsequent sintering process, the glass particles are bonded together by sintering, while the polymer support structure burns away. This also results in a porous, three-dimensional web framework, the geometry of which depends on the geometry of the polymer support structure. It is evident that, depending on the shape of the polymer support structure, any desired support geometry can be produced.

[0038] Particularly preferably, the framework has a maximum alkaline earth metal oxide content of 2.0% by mass and is reduced in its alkali metal oxide content, at least superficially, preferably over the entire cross-section of the framework, by leaching. Such a framework is particularly advantageous because it does not have a hydroxyapatite layer and is, on the one hand, very well suited for cell growth, and on the other hand, also dissolves readily in in vivo applications. Such a framework is described in detail in DE 10 2018 114 946 B3. Reference is expressly made to this publication, whereby the entire disclosure content relating to the bioactive carrier or framework, the production of a bioactive carrier with such a leached framework, the materials that can be used, and the corresponding manufacturing processes, etc., is explicitly incorporated into the present disclosure.

[0039] In addition to the bioactive carrier itself, the invention further relates to a method for producing a bioactive carrier, comprising the steps of: a) Providing a porous three-dimensional glass framework, b) Creating a porous reinforcing structure for the web framework from a synthetic polymer that can be released in the human or animal body, according to claim 16 or claim 22.

[0040] The process is therefore characterized by two key steps: firstly, the provision of the corresponding glass framework made of biodegradable glass, which can dissolve in the human or animal body. Different types of glass can be used as long as this requirement is met. Preferably, but not exclusively, a framework such as that disclosed in DE 10 2018 114 946 B3 is used, as already described.

[0041] In the second key step, the porous reinforcement structure that strengthens the bridge framework is applied, and this structure is also made of a material that is biocompatible in the human or animal body, i.e., non-toxic and biodegradable. According to the invention, a synthetic polymer is used for this purpose.

[0042] A polylactide is preferably used as the synthetic polymer, and within this group, poly(L-lactide), poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide) or poly(D,L-lactide-co-glycolide) is preferably used as the polymer.

[0043] From a manufacturing perspective, two fundamentally different production variants are conceivable with regard to the application or creation of the reinforcement structure. According to a first alternative of the invention according to claim 16, a fiber structure is applied to the outside of the web framework, preferably on all sides, as a reinforcement structure in the form of a wrapping. Accordingly, a very thin polymer fiber is placed around the web framework, the fiber structure essentially encasing it, whereby the degree of wrapping is naturally very low with regard to the actual covered area, which is preferably a maximum of 10%. This ensures that, viewed from the outside, the wrapped support remains extremely open-pored, so that during cell colonization, the relevant solutions, etc., can penetrate the support volume and the cells can colonize it.

[0044] In a further refinement of this inventive variant, it is provided that a polymer thread is drawn or spun from a polymer solution, which is then spun around the web framework, after which, optionally following drying, a heat treatment is carried out. Thus, a polymer solution is first prepared, consisting, for example, of double-distilled water, 1,4-dioxane, and the desired polymer, for example, polylactide, which is added at a mass percentage of 2–10%. The ratio of water to dioxane should be, for example, 13:87, although the water content can also be higher or lower, down to a minimum of 0% by mass. 1,4-Dioxane is a suitable solvent, and other organic solvents can also be used, optionally as an admixture to 1,4-dioxane.

[0045] After preparing the polymer solution, the appropriate polymer fiber is drawn and spun around the backbone. This can be done manually, especially on a laboratory scale, but preferably by machine on a larger scale. If necessary, drying can then be carried out to drive off the water, followed by heat treatment to remove the dioxane (the solvent) and crosslink the polymer. This heat treatment therefore involves tempering.

[0046] The polymer solution can be heated to a temperature of 40–90°C to draw the polymer fiber. The heat treatment should be carried out at a temperature of 50–200°C for 0.2–4 hours.

[0047] The drawn polymer fiber should have a diameter of 2 - 100 µm, in particular 5 - 75 µm and preferably 10 - 50 µm, taking into account during the production of the polymer fiber that shrinkage of approximately 20% may occur during drying / sintering due to the loss of water and dioxane.

[0048] One specific manufacturing variant looks like this, for example: 1. Provision of a web framework made of biodegradable glass, in particular according to DE 10 2018 114 946 B3, 2. Prepare a polymer solution from double-distilled water and 1,4-dioxane in a ratio of approximately 13:87, as well as the desired polymer (polylactide), and temper the solution to a temperature of 40–90°C so that a viscous, drawable or spinnable polymer solution is obtained. 3. Drawing or spinning a polymer fiber from the solution and wrapping the polymer fiber around the porous, three-dimensional web framework such that the polymer fiber is completely wrapped multiple times around the web framework, the wrapping preferably taking place on all sides of the web framework, 4. Drying the wrapped frame in air for several hours at room temperature, 5. Heat treatment of the web framework including polymer fibers at 50 - 200°C for 0.2 - 4 h for tempering.

[0049] This procedure is merely an example, but not a limiting one.

[0050] According to a second fundamental alternative of the invention according to claim 22, the reinforcing structure is also designed as a fiber structure, preferably forming a continuous fiber framework, within the web framework. Accordingly, corresponding polymer fibers are formed within the three-dimensional web framework, which preferably connect or cross-link to form a continuous fiber framework, i.e., an internal polymer framework, so that a quasi-double framework structure is created consisting of the glass framework and the quasi-integrated, stiffening polymer framework.

[0051] In a further refinement of this process variant, the framework can be impregnated with a polymer solution. After optionally removing the polymer solution from the surface of the framework, the impregnated framework is immersed in water, causing the polymer to precipitate as a foam. Following this, and optionally after drying, a heat treatment is carried out. Impregnation of the framework with the polymer solution introduces the polymer into the interior of the framework. The polymer solution is preferably a mixture of double-distilled water and 1,4-dioxane in a ratio of approximately 13:87, with the desired polymer, preferably polylactide, at a concentration of 2–10% by mass. However, the water content can also be reduced to zero, as water is not essential within the polymer solution for polymer precipitation in a subsequent process step.

[0052] After impregnation, if necessary, the polymer solution is drawn from the surface of the bridge structure and to a small extent also from the immediately adjacent volume, for example using an absorbent cloth or the like, which serves to avoid any skin formation that could lead to a sometimes extensive pore closure.

[0053] In the next step, the impregnated scaffold is immersed in water to reduce the solubility limit, causing the polymer to precipitate in a foam-like manner within the scaffold's volume. Following this precipitation, a drying step can optionally be performed; however, in any case, heat treatment is carried out to transform the scaffold-like structure of the foam-like precipitated polymer into cross-linked polymer fibers in a process similar to sintering. These fibers then extend from scaffold to scaffold or run along the scaffolds, preferably forming a connected fiber scaffold structure.

[0054] Here too, a heated polymer solution can be used, with a temperature of 20–90°C. The water into which the impregnated carrier is placed should have a temperature of 10–95°C, while the heat treatment should be carried out at a temperature of 50–200°C for 0.2–4 hours, with the temperature during the heat treatment being higher than the water temperature.

[0055] A specific manufacturing route for forming such an internal polymer framework structure can look like this: 1. Provision of a web framework made of biodegradable glass, in particular according to DE 10 2018 114 946 B3, 2. Prepare a polymer solution from double-distilled water and 1,4-dioxane in a ratio of approximately 13:87, as well as the desired polymer (polylactide), and temper the polymer solution to a temperature of 20–90°C. 3. Soaking the bridge structure with the polymer solution, 4. If necessary, remove the polymer solution from the surface or the outside of the web framework. 5. Immersion of the impregnated scaffold in water with a water temperature of 10 - 95° C to reduce the solubility of the polymer solution and precipitate a polymer foam forming a polymer scaffold structure. 6. Drying the frame in air for several hours at room temperature, 7. Heat treatment of the web framework with precipitated foam-like polymer scaffold structure at 50 - 200° C and 0.2 - 4 h, wherein the temperature during heat treatment is higher than the water temperature.

[0056] An alternative method for generating an internal polymer framework involves impregnating the framework with a polymer solution. Cooling then occurs to determine the solubility limit, causing the polymer to precipitate as a foam. This is followed, optionally after drying, by heat treatment. Here, too, a polymer solution as described above (double-distilled water, 1,4-dioxane, polymer) is used to impregnate the framework made of biodegradable glass. Unlike the previous method, where the impregnated framework is immersed in water to determine the solubility limit, here the solubility limit is reached by cooling, causing the polymer to precipitate as a foam. After optional drying, heat treatment is also performed to form the cross-linked polymer fibers within the framework through final sintering.

[0057] The polymer solution is at a higher temperature, for example, 50–90°C. Cooling is carried out as rapidly as possible to below the azeotropic point of the polymer solution, ideally 5–10 K below this azeotropic point, followed by a holding period. The heat treatment itself is then carried out at a temperature of 50–200°C for 0.2–4 hours.

[0058] A specific manufacturing route for this third variant could be as follows: 1. Provision of a web framework made of biodegradable glass, in particular according to DE 10 2018 114 946 B3, 2. Prepare a polymer solution from double-distilled water and 1,4-dioxane in a ratio of approximately 13:87, as well as the polymer (polylactide) at 2-10% by mass, and temper the polymer solution to 50-90°C. 3. Soaking the bridge structure with the polymer solution, 4. If necessary, remove the polymer solution from the surface of the web framework, 5. Rapid cooling of the impregnated scaffold below the solubility limit, preferably 5-10 K below the azeotropic point, and holding at this temperature for 5-120 min to precipitate a polymer foam forming a polymer scaffold structure. 6. Drying the frame in air for several hours at room temperature 7. Heat treatment of the web framework with polymer scaffold structure at 50 - 200°C for 0.2 - 4 h.

[0059] The internal polymer reinforcement structure or the polymer fiber framework should be designed in such a way that the porosity of the finished support, including the polymer framework, is at least 80%.

[0060] It is also conceivable that both an outer and an inner fiber structure are formed, meaning that both manufacturing techniques are used. Preferably, the inner fiber structure is produced first, followed by the outer one.

[0061] According to a particularly advantageous embodiment of the invention, a glass framework with a maximum alkaline earth metal oxide content of 2% by mass can be used, wherein the framework is acid-treated before or after the formation of the polymeric reinforcement structure to at least superficially reduce the alkali metal oxides. A framework as described in DE 10 2018 114 946 B3 is therefore preferably used. The leaching of the glass framework can take place before the formation of the polymeric reinforcement structure, either if the polymer cannot withstand acid attack for leaching, or if the framework is still manageable despite leaching in order to carry out the subsequent steps for applying the polymeric reinforcement structure, such as mechanical over-spinning or similar processes.Preferably, however, the leaching is carried out after the application of the polymer reinforcement structure, since the polylactides used in particular are sufficiently acid-stable and are not damaged by an acid attack used for leaching. Because the matrix is ​​not yet leached, it is easy to handle for creating the polymer reinforcement structure, which simplifies manufacturing.

[0062] The web framework, with or without the reinforcing structure, is preferably leached with hydrochloric acid, preferably a 0.1 molar hydrochloric acid solution. The temperature of the hydrochloric acid can be, for example, approximately 37°C, and the acid attack can extend over several hours or days, depending on the degree of leaching.

[0063] In addition to the polymer reinforcement framework, the glass web framework naturally plays a central role. This can be manufactured in various ways. One possibility is to use a web framework made of glass fibers bonded together by sintering. The fibers can be laid or spun individually, or prefabricated fiber mats, fabrics, or similar materials can be used and layered on top of each other. The individual fibers are then firmly bonded together at the corresponding contact points by sintering. Any carrier geometry is conceivable, as the fibers can be spun or cut and layered in any geometrically desired way.

[0064] Alternatively, a framework made of sintered glass powder can be used, which is first applied in suspension to a polymer support structure and then sintered. During this process, the glass particles bond together while the support structure burns away, forming a corresponding framework structure. However, the manufacturing options are not limited to this; other methods are also conceivable.

[0065] Further advantages and details of the invention will become apparent from the exemplary embodiments described below and from the drawings. These show: Fig. 1 A view of a bioactive carrier with a web framework and an external reinforcement structure created by wrapping before heat treatment, Fig. 2 a SEM image of the carrier from Fig. 1, Fig.3 a perspective view of a bioactive carrier of a second embodiment with a web framework formed from individual glass fibers and a reinforcement structure in the form of a sheathing, Fig. 4 a SEM image of the carrier from Fig. 3, Fig. 5 a perspective view of a bioactive carrier of a third embodiment with a polymeric reinforcement structure formed inside the glass carrier before heat treatment, Fig. 6 a SEM image of the carrier from Fig. 5, Fig. 7 a SEM image of the carrier from Fig. 5 after the heat treatment has been carried out, Fig. 8 a SEM image of a web framework formed from individual glass fibers with a polymeric reinforcing structure formed therein after heat treatment, Fig. 9 A force-displacement diagram to illustrate the behavior of different bioactive carriers with and without polymeric reinforcement structure. Fig. 10. A representation of a support without a polymer reinforcement structure after the load test. Fig. 11. A representation of a carrier with a reinforcement structure in the form of a wrapping after the load test. Fig. 12. A representation of a support with an internal polymeric reinforcement structure after the load test. Fig. 13 a laser scanning microscope image of a carrier colonized with porcine articular chondrocytes with an external reinforcing structure in the form of a cocoon, after 7 days in culture, Fig. 14 of the same carrier with porcine articular chondrocytes after 28 days in culture, Fig. 15 a laser scanning microscope image of a support with a polymer reinforcement structure in the form of a sling and human mesenchymal stromal cells seeded on it after 7 days in culture, Fig.16 the same carrier with stromal cells after 28 days in culture, Fig. 17 a carrier with an internal polymeric reinforcement structure and human mesenchymal stromal cells seeded on it after 7 days in culture, and Fig. 18 the same carrier with stromal cells after 28 days in culture.

[0066] Fig. Figure 1 shows a bioactive support 1 of a first embodiment for the seeding of living cells. The support consists of a porous three-dimensional web framework 2 made of glass (see in particular Figure 1). Fig. 2), which was manufactured in accordance with DE 10 2018 114 946 B3. It is a virtually random glass web framework with a porosity > 80%, where the webs have, for example, a thickness of 30–120 µm. As will be discussed below, the webs are surface leached to reduce the alkali metal oxide content, for which purpose a treatment with hydrochloric acid was carried out.

[0067] On the outside, surrounding the web framework 2, a reinforcing structure 3 made of a synthetic polymer, which is biocompatible and soluble in the human or animal body, was applied in the form of a fiber structure 4 by wrapping, wherein this fiber structure 4 or wrapping consists of one or more individual polymer fibers 5 completely wound around the web framework 2.

[0068] To produce this fiber structure, or rather, to create the over-spinning, a polymer solution containing 10 wt% of the polymer and 1,4-dioxane was prepared. A polylactide, specifically poly(D,L-lactide-co-glycolide), was used as the polymer. The polymer solution was heated to 70°C. Subsequently, fibers with a thickness of 5–80 µm were drawn from the solution using a syringe tip and wound around the web framework 2, i.e., the bioglass scaffold. The web framework 2 was completely over-spun, while still maintaining a sufficiently large open pore volume (see figure). Fig.2, remains to allow cells to settle inside as well.

[0069] After complete wrapping, the product was dried at room temperature for approximately 6 hours.

[0070] Fig. Figure 1 shows the carrier 1 after the drying step. The polymer fibers are still somewhat thicker; they do not yet have the final geometry that they will only acquire after a subsequent heat treatment.

[0071] This heat treatment was carried out at 60°C for 30 minutes. It leads to the expulsion of the dioxane and the final cross-linking of the polymer fiber, causing it to shrink and assume its final shape, as seen in... Fig.2 is shown in the enlarged microscopic image. The polymer fibers 5 are clearly visible, extending in the form of coils around the web framework 2, thus encircling it, but not significantly reducing the open pore volume on the outside of the web framework 2. They form a kind of firm yet elastic cocoon around the web framework, which makes the support 1 considerably more stable against any shear or compressive loads.

[0072] Fig. Figure 3 shows a second embodiment of a bioactive carrier 1, where the same reference numerals are used for identical components. Here, too, a web framework 2 is used, which was manufactured according to DE 10 2018 114 946 B3, i.e., which was also surface-leached. However, it does not consist of a quasi-sponge-like structure, but was made of individual, randomly arranged glass fibers 6 (cf. Figure 3). Fig.6), which were sintered together. Independently of this, a reinforcement structure 3 in the form of a fiber structure 4 consisting of wound polymer fibers 5 is also provided here, which in turn are spun around the outside of the web framework 2.

[0073] While Fig. Figure 3 shows the carrier 1 after wrapping and drying, the enlarged microscope image according to Fig. 4. The carrier 1 is shown in section after heat treatment, which also took place at 60°C for 30 minutes. It is evident that a stable outer fiber framework is formed here as well, which surrounds and stiffens the glass web framework 2 on the outside.

[0074] The polymer solution used was the same as in the embodiment according to the Fig. 1 and Fig. 2 described.

[0075] The Fig.Figures 5-7 show a further embodiment of a bioactive support 1, in which the reinforcing structure is designed as a polymer fiber structure formed inside the three-dimensional web framework 2 or as a polymer framework. This support 1 also has a glass web framework 2, which is a one-piece three-dimensional web framework and was again manufactured according to DE 10 2018 114 946 B3.

[0076] Here, too, a polymer solution is prepared, which in the example shown contains 5 wt% polymer (poly(D,L-lactide-co-glycolide)) in a water / 1,4-dioxane mixture with a ratio of 13:87. The solution is applied dropwise to the scaffold 2 (the bioglass scaffold) using a syringe at approximately 50–60°C, allowing the solution droplets to sink in. Once the scaffold 2 is saturated with the polymer solution, it is placed on absorbent paper, which removes the polymer solution from the scaffold surface and partially from the adjacent interior. This serves to prevent any skin formation on the surface, which could lead to at least partial pore closure on the outside.

[0077] The impregnated framework is then quickly placed in a water bath heated to 50°C, which is positioned on a heated hot plate. After approximately 40 seconds, the framework is removed and placed on absorbent paper for pre-drying, after which final drying takes place at room temperature.

[0078] When the impregnated bridge structure is placed in the water bath, the solubility limit is undercut, leading to precipitation of the polymer in a foam-like consistency or form. Fig. Figure 5 shows an image of the substrate after drying, in which the polymeric reinforcement structure 3 is visible in the form of the not yet fully cross-linked fiber framework. Relatively large zones with a foam-like polymer framework structure are still present, as also seen in the SEM image in Fig. 6 are shown. Fig.Figure 6 also shows that this reinforcement structure, or polymer foam structure, forms both on the surface and in the interior.

[0079] After drying, a heat treatment is carried out by heating the dried web frame 2 to 95°C and holding it for approximately 30 minutes, after which it cools down. Fig. Figure 7 shows an enlarged SEM image of the support 1 with the now fully formed polymeric reinforcement structure 3, which forms a fiber structure 4 whose fibers 5 extend from web to web and essentially connect them. Nevertheless, the open porosity is ensured, as Fig. Figure 7 shows. The fibers 5 have, similar to the design according to the Fig. 1 - 4, a diameter or thickness of approximately 2 - 100 µm.

[0080] Fig.Figure 8 shows an embodiment of a support 1 in the form of an SEM image, again comprising a web framework 2, which here is formed from a plurality of individual glass fibers 6 that are bonded together by sintering. This web framework 2 is also surface leached to reduce the alkali metal oxide content.

[0081] Here too, a reinforcement structure 3 in the form of an internal polymer framework structure is formed, which is constructed using the same polymer solution and the same procedure as in the embodiment according to the Fig. 5 - 7 was manufactured. Fig. Figure 8 shows the support 1 after heat treatment, in which the formerly foam-like polymer scaffold structure has been transformed into the finished fiber structure 4 with the individual polymer fibers 5 connecting the webs formed over the fibers 6.

[0082] As described in the introduction, the web framework is leached via an acid attack to reduce the alkali metal oxide concentration, at least superficially. This acid treatment can be carried out either before the application of the reinforcing structure 3, i.e., before the over-spinning, or before the formation of the inner polymer framework structure, provided the web framework remains sufficiently stable and thus manageable after this acid treatment, and the application of the reinforcing structure 3 proceeds without difficulty. Should the acid attack lead to an unstable web framework due to the delicate nature of the web structure 2, this leaching can also take place after the application of the polymeric reinforcing structure 3, i.e., after completion of the final heat treatment. This is because the preferably used polylactides, which are employed to form the polymeric reinforcing structure, are stable against such an acid attack, for example, using 0.1 molar hydrochloric acid.They therefore suffer no damage from the acid attack and still possess their mechanical properties.

[0083] As described, the creation of the polymeric reinforcement structure 3 serves to make the carrier 1 more stable, so that it withstands potential mechanical stresses better than a carrier without a polymeric reinforcement structure, i.e., one consisting only of the glass framework. The aim of the polymer reinforcement is to ensure that, when an implant is used in the human body, it retains its shape under stress and resists the load.

[0084] To demonstrate this, three different supports were produced. All three supports examined feature the same bioglass web framework. For this purpose, a bioglass as described in DE 10 2018 114 946 B3 was used and processed accordingly to produce a leached bioglass web framework, as described in this publication. Example 1:

[0085] In this embodiment, the pure glass web framework was used as the support. The web framework, manufactured according to DE 10 2018 114 946 B3, was treated with 0.1 molar hydrochloric acid at 37°C for 5 days at a constant pH of 1, without the application of a polymeric reinforcement structure. Example II:

[0086] In this embodiment, the glass web framework according to DE 10 2018 114 946 B3 was provided with a reinforcing structure in the form of a fiber structure created externally by wrapping before leaching.

[0087] For this purpose, a polymer solution was prepared containing 10 wt% polymer (poly(D,L-lactide-co-glycolide), double-distilled water, and 1,4-dioxane (ratio 13:87), which was heated to 70°C. Fibers with a diameter of 5–80 µm were drawn from the solution using a syringe tip and wound around the bioglass framework.

[0088] After complete wrapping, the structure was dried at room temperature for 6 hours and then heat-treated at 60°C for 30 minutes. Following this heat treatment, the web framework, including the polymer reinforcement, was treated with 0.1 molar hydrochloric acid at 37°C for 5 days at a constant pH of 1. Example III:

[0089] Here too, a bioglass framework according to DE 10 2018 114 946 B3 was used, which was provided with an internally formed polymer reinforcement structure before leaching. For this purpose, a polymer solution containing 5 wt% poly(D,L-lactide-co-glycolide) and a mixture of double-distilled water and 1,4-dioxane in a ratio of 13 : 87 was prepared.

[0090] The solution was then applied dropwise to the bioglass scaffold using a syringe at approximately 60°C, allowing the solution droplets to sink in. After the scaffold was completely saturated, it was placed on absorbent paper to remove the polymer solution from the scaffold surface and surrounding areas, preventing skin formation. The saturated scaffold was then placed in a water bath at approximately 50°C, which was positioned on a heated plate. After approximately 40 seconds, the scaffold was removed and placed on absorbent paper for pre-drying, after which it was dried completely at room temperature. This was followed by a heat treatment at 60°C for 30 minutes to form the final polymer scaffold integrated within the glass scaffold.After this treatment, the support, including the polymer framework reinforcement, was treated with 0.1 molar hydrochloric acid at 37°C for 5 days at a constant pH of 1.

[0091] These three different supports were then subjected to a load test, in which a stamp was applied to each support with a defined force. The result is in Fig. 9 is shown, where in Fig. 9. Along the abscissa, the compression in µm, i.e., the path of the pressure stamp with which pressure is applied to the carrier, is plotted, while along the ordinate, the force in mN is plotted.

[0092] Three curves I, II, III are shown, corresponding to embodiments I, II, III.

[0093] Curve I shows the force-displacement curve for embodiment I, i.e., for the unreinforced, leached beam consisting only of the glass web framework. It can be seen that compressive stress on the leached web framework causes the webs to break continuously, as clearly illustrated by the jagged shape of curve I over the compression path. The webs break even under relatively low loads; no elastic behavior is observed. The web framework breaks apart and is forced apart, leaving many individual pieces at the end of the test.

[0094] Fig. Figure 10 shows a photograph of the support 1 according to embodiment I after the test has been carried out. The glass support 1 is clearly broken into a multitude of small individual pieces.

[0095] Curve II shows the force-displacement curve of a leached web framework with a polymer reinforcement structure obtained through over-spinning. The curve shows that the web framework can be easily compressed at the beginning of the compaction, but then the effect of the over-spinning takes over as framework stabilization. Disintegration or expansion of the web framework is prevented, and increased resistance to compaction is achieved. The absence of a jagged edge compared to Curve I indicates that fracture of the web framework does not occur. This is also evident in the Fig.Figure 11 shows the support 1 according to embodiment II after the test has been carried out. The support 1 shows no impairment or damage whatsoever; the glass web framework 2 is intact, and the support 1 therefore retains its shape. Fracture is avoided, and dimensional stability is ensured by the elastic behavior and the stiffening provided by the polymer reinforcement structure 3.

[0096] A similar, even slightly better, result is shown by curve III for embodiment III. This support has a polymer reinforcement structure integrated into the glass web structure; that is, a polymer reinforcing web framework is integrated into the glass web framework. The shape of curve III shows that the web framework exhibits comparatively elastic behavior after the start of loading, consequently providing framework stabilization and, as the steep curve towards the end shows, achieving increased resistance to further compression. Here, too, the absence of a jagged edge compared to curve I indicates that fracture of the glass web framework does not occur. This is also shown here. Fig. 12, which shows the support 1 with its web framework 2 and the integrated polymer framework 3 in undamaged form after the test has been carried out.

[0097] Thus, the integration of the polymeric scaffold-like reinforcement structure 3 also achieves a significant stiffening and stabilization of the leached glass web scaffold 2, giving the support 1 an elastic behavior that ensures shape stability.

[0098] As described, a bioactive carrier according to the invention with polymer reinforcement serves to colonize and multiply living cells on it. To demonstrate that this is successful, colonization experiments were carried out on various carriers 1, which were produced according to embodiments II and III either with fiber wrapping or with an integrated polymer fiber scaffold structure, using different cells.

[0099] The cell types used were either porcine articular chondrocytes (pGC) or mesenchymal stromal cells from human bone marrow (hMSC).

[0100] To carry out the experiments, appropriately prepared cell suspensions were pipetted onto appropriately prepared, inventive bioactive supports and then incubated in an incubator.

[0101] The procedure was as follows: - Place the bioactive carriers under the sterile workbench into a sterile 50 ml bioreactor tube with a filter cap. - Treatment of the cells intended for scaffold colonization (pGC and hMSC) after a rinsing step with PBS for 5 min in an incubator with trypsin / EDTA solution (0.05 / 0.02%) to detach the cells from the culture medium of the cell culture flasks used for cell proliferation - pGC: Addition of 5 ml of culture medium containing 10% fetal calf serum (FCS) (Ham's F-12 / Dulbecco's Modified Eagle's [DMEM] Medium 1:1), 10,000 IU / mL penicillin / 10,000 µg / mL streptomycin, 2.5 µg / ml amphotericin B, non-essential amino acids and 25 µg / ml ascorbic acid - hMSC: Addition of 5 ml of stem cell-specific expansion medium (FG0445 / Dulbecco's Modified Eagle's [DMEM] / HG) with 5% platelet lysate (PL), 50 IU / ml streptomycin, 50 IU / ml penicillin, - 2.5 µg / ml amphotericin B, 100 mM sodium pyruvate and 5000 U / ml heparin - Stopping the detachment process by adding 5 ml of 10% FCS-containing medium, whereby the FCS or the PL terminates the enzymatic activity of the trypsin. - Centrifugation of the cell suspension at 300 rpm or 484 g for 5 min - Resuspension of the cell pellet resulting from centrifugation in 1 ml of culture medium - Mix 10 µl of trypan blue solution (1%) with 10 µl of cell suspension so that dead cells stain. - Pipette 10 µl of this mixture into a Neubauer counting chamber and count the living cells. - Pipette the cells at a concentration of 500,000 to 1,000,000 cells per scaffold in a volume of 1 mL per scaffold. - After 20 minutes, top up the culture medium to 10 ml volume to ensure a sufficient supply for the subsequent dynamic culture. - Cultivation of the colonized bioactive carriers in an incubator at 37 °C and 5% CO2 on an orbital shaker (dynamic) - For longer incubation periods, change the culture medium every two days.

[0102] To verify that the polymer reinforcement had no negative effects, laser scanning microscope images of the in vitro culture were taken after various time periods / days, requiring viability staining. This was performed as follows: - Preparation of a vitality staining solution from 15 µg / ml fluorescein diaacetate (FDA) and 10 µg / ml propidium iodide (PI) dissolved in PBS - Extraction of the respective bioactive carrier from the dynamic cultivation in the incubator - Pipette 50 µl of vitality solution onto the colonized bioactive carrier - Examination of the cells: on the bioactive carrier, living cells can be differentiated green and dead cells red due to the staining with the vitality solution using a confocal laser scanning microscope.

[0103] PBS serves as a buffer, and FDA is used as the dye. This dye penetrates living cells and is enzymatically converted into a fluorescent compound, which is excited at a wavelength of 525 nm. Pl intercalates into the DNA of dead cells because their cell and nuclear membranes become permeable to it. Pl is excited at a wavelength of 600 nm.

[0104] The corresponding results are in the Fig. 13 - 18 shown.

[0105] Basically, the Fig. 13-18 The light areas are the regions in or on carrier 1 that are colonized with living, multiplying cells 8. The dark areas are primarily uncolonized parts of carrier 1.

[0106] Fig. Figure 13 shows a representative viability image of porcine articular chondrocytes after 7 days in culture, which are located on a bioglass scaffold with a polymer reinforcement formed by overlay. For example, a ridge 7 of the scaffold 2 is visible, on which cells 8 have settled. Also visible is a pore 9 within the scaffold 2, as well as an imprint of a polymer fiber 5 in the cell layer. A polymer fiber 5 colonized with cells 8 is also visible.

[0107] Fig. 14 shows the carrier made of Fig. 13 with the porcine articular chondrocytes colonizing it after 28 days in culture. Cell growth has continued continuously, and the bioactive scaffold is more densely populated.

[0108] Fig.Figure 15 shows a representative vitality image of human mesenchymal stromal cells after 7 days in culture, which were also grown on a bioglass scaffold with polymer reinforcement formed by spinning, i.e., on the same support as in the Fig. 13 and Fig. 14.

[0109] Fig. Figure 15 shows that this other cell type spread significantly over a larger area after the same culture period (7 days) than the articular chondrocytes according to the Fig. 13. Almost complete closure of the pores of the web framework, which can no longer be precisely identified as such, is already evident after 7 days. A larger pore 9 and several smaller pores 9 of the web framework are also visible, as are impressions of the polymer fibers 5 within the cell layer.

[0110] Fig. 16 shows the carrier made of Fig.15 with mesenchymal stromal cells after 28 days in culture. Individual cells are barely recognizable. The entire support 1 is almost completely filled with grown cells; the cell lawn now covers the surface of support 1.

[0111] Both experiments show that a carrier reinforced by spinning is ideally suited for colonization with cells and their proliferation, with different cell types growing at different rates.

[0112] Fig. Figure 17 shows a representative vitality image of human mesenchymal stromal cells after 7 days in culture on a bioglass scaffold with integrated polymer reinforcement produced from a foam precipitation.

[0113] Fig. 18 shows the carrier from Fig. 17 after 28 days in culture. A comparison of Fig. 17 and Fig.18. The increase in cell area over time is clearly visible. Larger cell clusters form after just 7 days on both the glass bridges and the polymer fibers, as seen in the light spots in Fig. Figure 17 shows that these cell clusters increase significantly after 14 days in culture, meaning that a carrier with integrated polymer reinforcement is also very well suited for the settlement and multiplication of cells.

[0114] The following is a list of the materials and equipment used in the colonization experiments and vitality assessments: Material / Equipment Order number company HERAcell 150i incubator Thermo Electron LED GmbH, DE Centrifuge 5810 R Eppendorf AG, DE Diavert microscope Leitz GmbH, Wetzlar, Germany Dulbecco's Modified Eagle's Medium FG4815 Biochrom AG, DE Essential amino acids, 50x MEM-AS K0363 Biochrom AG, DE Ethidium bromide solution, 1% 2218.1 Carl Roth GmbH & Co.KG, DE Fetal calf serum (FBS superior) S0615 1000F Biochrom AG, DE Fluorescein diaacetate (FDA) F7378-5G Sigma-Aldrich, USA Heraeus Multifuge X1R Centrifuge Thermo Elektron LED GmbH, DE Confocal laser scanning microscope DMi8 Leica, Wetzlar, Germany Neubauer counting chamber, improved Brand, DE Paraformaldehyde, 4% (PFA) USBM199431LT VWR, DE Penicilin-streptomycin (10,000 U / ml / 10,000µg / ml) A2212 Biochrom AG, DE Phosphate Buffered Saline (PBS) L1825 Biochrom AG, DE Orbital shaker, SU1400 for dynamic scaffold cultivation Sustainable Lab Instruments, DE HERAsafe KS sterile workbench Thermo Elektron LED GmbH, DE TBS (Tris Buffered Saline) 09-7500-10 Medicago, SWE In tablet form: - Trypan blue, 1% L6323 Biochrom AG, DE - Trypsin / EDTA L2153 Biochrom AG, DE Tubespine® Bioreactor 50 (50 ml Volume) Cell culture vessels for dynamic culture TPPO, CH Vitamin C (Ascorbic acid) A5960 Sigma-Aldrich, USA Cell culture bottle Cell plus T25 / T75 / T175 Sarstedt AG, DE

Claims

[1] Bioactive carrier for the settlement of living cells, with a porous three-dimensional framework (2) made of glass, characterized by a porous reinforcing structure (3) made of a synthetic polymer that is soluble in the human or animal body, wherein the reinforcing structure (3) is a fiber structure (4) surrounding the web framework (2) on the outside. [2] Bioactive carrier according to claim 1, characterized by , that the reinforcement structure (3) is designed in the form of a wrapping around the web framework (2). [3] Bioactive carrier according to claim 2, characterized by , that the wrapping encloses the web frame (2) on all sides. [4] Bioactive carrier according to any of the preceding claims, characterized by , that the surface area covered by the fiber structure (4) is at most 10%. [5] Bioactive carrier according to any of the preceding claims, characterized by, that the fibers (5) of the fiber structure (4) have a diameter of 2-100µm, in particular of 5-75µm and preferably of 10-50µm. [6] Bioactive carrier for the settlement of living cells, with a porous three-dimensional web framework (2) made of glass, characterized by a porous reinforcing structure (3) made of a synthetic polymer that is soluble in the human or animal body, wherein the reinforcing structure (3) is a fiber structure (4) formed inside the web framework (2), wherein the fiber structure (4) is a fiber framework structure that is at least partially interconnected [7] Bioactive carrier according to claim 6, characterized by that the porosity is at least 80% [8] Bioactive carrier according to one of claims 1 to 5 and one of claims 6 or 7, characterized by, that both a reinforcement structure in the form of a fiber structure (4) surrounding the web framework on the outside and a reinforcement structure in the form of a fiber structure (4) formed inside the web framework is provided. [9] Bioactive carrier according to any of the preceding claims, characterized by that the polymer is a polylactide. [10] Bioactive carrier according to claim 9, characterized by that the polymer is poly(L-lactide), poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide) or poly(D,L-lactide-co-glycolide). [11] Bioactive carrier according to any of the preceding claims, characterized by , that the web framework (2) has a porosity of at least 80%. [12] Bioactive carrier according to any of the preceding claims, characterized by , that the pore size of the web framework (2) is between 20-300 µm, in particular 50-200 µm. [13] Bioactive carrier according to any of the preceding claims, characterized by, that the webs of the web framework (2) have a thickness of 10-400 µm, in particular 20-200 µm, preferably between 50-150 µm. [14] Bioactive carrier according to any of the preceding claims, characterized by , that the web framework (2) consists of glass fibers (6) connected to each other by sintering or of sintered glass powder. [15] Bioactive carrier according to any of the preceding claims, characterized by , that the web framework (2) has a content of alkaline earth metal oxides of a maximum of 2.0 wt% and is reduced in its content of alkali metal oxides at least superficially, preferably over the web cross-section, by leaching. [16] Method for producing a bioactive carrier, comprising the steps: a) Providing a porous three-dimensional web framework (2) made of glass, b) Producing a porous reinforcing structure (3) to reinforce the web framework (2) from a synthetic polymer that is soluble in the human or animal body, wherein the reinforcing structure (3) is a fiber structure (4) surrounding the web framework on the outside, preferably all sides, in the form of a wrapping around the web framework (2). [17] Method according to claim 16, characterized by that a polylactide is used as the polymer. [18] Method according to claim 17, characterized by that poly(L-lactide), poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide) or poly(D,L-lactide-co-glycolide) is used as the polymer. [19] Method according to any one of claims 16 to 18, characterized by , that the wrapping is applied in such a way that the covered surface area is a maximum of 10%. [20] Method according to any one of claims 16 to 19, characterized by, that a polymer fiber (5) is drawn or spun from a polymer solution, which is then spun around the web framework (2), after which, if necessary after drying, a heat treatment is carried out. [21] Method according to claim 20, characterized by that a polymer solution heated to a temperature of 40-90°C is used and / or the heat treatment takes place at a temperature of 50-200°C for 0.2-4 h. [22] Method for producing a bioactive carrier, comprising the steps: a) Providing a porous three-dimensional web framework (2) made of glass, b) Generating a porous reinforcing structure (3) reinforcing the web framework (2) from a synthetic polymer soluble in the human or animal body, wherein the reinforcing structure (3) is a fiber structure (4) forming a fiber framework structure that is at least partially interconnected inside the web framework. [23] Method according to claim 22, characterized by , that the web framework (2) is impregnated with a polymer solution, after which, if necessary after removal of the polymer solution from the surface of the web framework (2), the impregnated web framework (2) is placed in water so that the polymer precipitates in a foamy form, after which, if necessary after drying, a heat treatment is carried out. [24] Method according to claim 23, characterized by that the polymer solution has a temperature of 20-90°C, and / or that the water has a temperature of 10-95°C and the heat treatment takes place at a temperature of 50-200°C for 0.2-4 h, whereby the temperature during the heat treatment is higher than the water temperature. [25] Method according to claim 22, characterized by , that the web framework (2) is impregnated with a polymer solution, after which cooling takes place so that the polymer precipitates in a foam-like form, after which, if necessary after drying, a heat treatment takes place. [26] Method according to claim 25, characterized by that the polymer solution has a temperature of 50-90°C and that cooling takes place below the azeotropic point of the polymer solution, and / or that the heat treatment takes place at a temperature of 50-200°C for 0.2-4 h. [27] Method according to any one of claims 22 to 26, characterized by , that the reinforcement structure (3) is designed such that the porosity of the carrier is at least 80%. [28] Method according to one of claims 16 to 21 and one of claims 22 to 27, characterized by , that both an outer fiber structure (4) and an inner fiber structure (4) are formed. [29] Method according to any one of claims 16 to 28, characterized by, that a web framework (2) made of glass is used which has an alkaline earth metal oxide content of at most 2 wt%, wherein the web framework (2) is acid-treated before or after generating the polymeric reinforcing structure to at least superficially reduce the alkali metal oxides. [30] Method according to claim 29, characterized by , that the web framework (2), with or without the reinforcing structure, is leached with hydrochloric acid, preferably 0.1 molar hydrochloric acid. [31] Method according to any one of claims 16 to 30, characterized by , that a web framework (2) with a pore size of 300µm, in particular 50-200µm and / or a web thickness of 10-400µm, in particular 20-200µm, preferably between 50-150µm is used. [32] Method according to any one of claims 16 to 31, characterized by , that a framework (2) made of glass fibers (5) connected to each other by sintering or of sintered glass powder is used.

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